Sunday, Feb 11, 2018
South San Francisco, CA -- February 11, 2018 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced encouraging results from the Phase II BOULEVARD study. In people with vision loss from diabetic macular edema (DME), treatment with intravitreal RG7716 resulted in clinically meaningful and statistically significant improvements in visual acuity gains compared with ranibizumab alone. Key secondary and exploratory anatomical outcomes – reduction of central retina thickness and improvements in diabetic retinopathy severity scores – were supportive of the primary outcome. RG7716 is the first bispecific, monoclonal antibody specifically designed for the eye that simultaneously binds to and inactivates vascular endothelial growth factor A (VEGF-A) and Angiopoietin-2 (Ang-2). These data were presented at Angiogenesis, Exudation, and Degeneration 2018, a medical symposium presented by Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine, part of the University of Miami Health System.1
“For the first time in diabetic macular edema, a clinically meaningful and statistically significant improvement in visual acuity compared to anti-VEGF alone has been demonstrated by simultaneously neutralizing both Angiopoietin-2 and VEGF-A with a bispecific antibody,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “These Phase II results show the potential of RG7716 for people living with diabetic macular edema, a leading cause of vision loss in working-age adults. There remains a significant unmet medical need for more efficacious and longer lasting therapies for diabetic macular edema.”
BOULEVARD assessed two doses of RG7716 (1.5 mg and 6 mg) versus ranibizumab standard of care (0.3 mg) given as monthly intravitreal injections. The study met its primary endpoint, demonstrating a significant improvement in adjusted Best Corrected Visual Acuity (BCVA) at week 24 for RG7716 versus ranibizumab in treatment-naïve patients: 6 mg RG7716 resulted in an adjusted mean improvement of 13.9 chart letters from baseline, compared to 11.7 letters in patients treated with 1.5 mg RG7716, and 10.3 letters in patients treated with 0.3 mg ranibizumab. The difference between 6 mg RG7716 and 0.3 mg ranibizumab was statistically significant with an adjusted mean difference of +3.6 letters (p=0.03, 80% CI 1.53-5.61, pre-specified significance level: p<0.2).
Secondary endpoints of the study included assessment of functional and anatomic measures versus ranibizumab standard of care. Both RG7716 arms achieved higher proportions of patients gaining more than two, and more than three, lines of visual acuity. Both RG7716 arms resulted in greater reduction of central retina thickness as well as a greater two-step improvement of diabetic retinopathy severity. RG7716 was well tolerated with no new safety signals observed. Additional data analyses of BOULEVARD are ongoing and will be presented at future medical meetings.
In addition to BOULEVARD, RG7716 is also being evaluated in the Phase II AVENUE and STAIRWAY studies in neovascular age-related macular degeneration (nAMD), also known as wet AMD. All three studies have finished enrollment and are currently in follow-up. Genentech is committed to presenting data from all Phase II studies at upcoming medical meetings, and we plan to discuss our Phase III program with the U.S. Food and Drug Administration (FDA) following data assessment.
A live audio webcast and conference call to discuss the data from the Phase II BOULEVARD study in DME will be held on Tuesday, February 13th from 7:00 to 8:00 a.m. PST. This virtual event, independently organized by Roche, is open to registered analysts and investors. To register for the event, please follow this link .
About the BOULEVARD Study
BOULEVARD (NCT02699450)2 is a Phase II study designed to assess the efficacy and safety of RG7716 compared with ranibizumab in people with diabetic macular edema (DME). This prospective, randomized, comparator-controlled, double-masked, multicenter, multi-dose, three-arm study enrolled 229 participants in more than 90 sites across the United States. All patients were dosed monthly (28 days +/– 7 days) for 20 weeks. Subsequently, there is an observation period of up to 16 weeks for a total study length of 36 weeks. The primary objective of BOULEVARD was to demonstrate superior gains in visual acuity compared to ranibizumab injections at week 24 in anti-vascular endothelial growth factor (VEGF) treatment-naïve participants.
RG7716 is the first bispecific, monoclonal antibody specifically designed for the eye that simultaneously binds to and neutralizes both Angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) with high potency and specificity. In diabetic macular edema (DME), Ang-2 works synergistically with VEGF to drive biological pathways that cause vessel permeability and inflammation. Both of these contribute to vascular instability which results in vision loss.3,4 Therefore, simultaneous inhibition of both Ang-2 and VEGF may lead to improved outcomes, reduced treatment burden, or both.3,4
About Lucentis® (ranibizumab injection)
Lucentis is a vascular endothelial growth factor (VEGF) inhibitor designed to bind to and inhibit VEGF-A, a protein that is believed to play a critical role in the formation of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels.
Lucentis is FDA-approved for the treatment of patients with wet age-related macular degeneration (AMD), macular edema after retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR) and myopic choroidal neovascularization (mCNV).
Lucentis was developed by Genentech, a member of the Roche Group. The company retains commercial rights in the U.S. and Novartis has exclusive commercial rights for the rest of the world.
Outside the U.S., Lucentis is approved in more than 110 countries to treat patients with wet AMD, for the treatment of DME, and due to macular edema secondary to both branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO) and visual impairment due to choroidal neovascularization (CNV).
Lucentis Important Safety Information
Patients should not use Lucentis if you have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.
Lucentis is a prescription medication given by injection into the eye, and it has side effects. Lucentis is not for everyone. Some Lucentis patients have had detached retinas and serious eye infections. If your eye becomes red, sensitive to light, or painful, or if you have a change in vision, call or visit your eye doctor right away.
Some patients have had increased eye pressure before and within 1 hour of an injection. Your eye doctor should check your eye pressure and eye health before and after your Lucentis injection.
Uncommonly, Lucentis patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes.
Fatal events were seen more often in patients with DME and DR with Lucentis compared with patients who did not receive Lucentis. Although there were only few fatal events which included causes of death typical of patients with advanced diabetic complications, these events may be caused by Lucentis.
Some Lucentis patients have serious side effects related to the injection. These include serious infections inside the eye, detached retinas, and cataracts. The most common eye-related side effects are increased redness in the white of the eye, eye pain, small specks in vision, and increased eye pressure. The most common non–eye-related side effects are nose and throat infections, anemia, nausea and cough.
Lucentis is for prescription use only.
Patients may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555.
For additional safety information, please see Lucentis full Prescribing Information, available here: http://www.gene.com/download/pdf/lucentis_prescribing.pdf
About Diabetic Macular Edema (DME)
Diabetic macular edema (DME) affects approximately 750,000 people in the United States and is associated with blindness and decreased quality of life when left untreated.5 Loss of visual function due to diabetes is the leading cause of adult onset blindness.6,7 The longer people have diabetes, especially if it is poorly managed, the higher their risk for developing DME. DME is one of the vision-threatening complications of diabetic retinopathy, in which chronic damage occurs to the fine blood vessels of the retina, the light-sensitive tissue at the back of the eye necessary for good vision.8
There is a significant unmet need for more efficacious and longer-lasting therapies for people with DME.9, 10, 11, 12, 13 DME is a multifactorial disease with a strong inflammatory component. While current anti-vascular endothelial growth factor (VEGF) treatments effectively address vessel permeability, they only partially address the inflammatory component of the disease. DME causes or leads to central vision loss, limiting a person’s ability to perform tasks essential for daily life, potentially resulting in increased social isolation and decreased mental health.14
About Genentech in Ophthalmology
Genentech is researching and developing new treatments for people living with a range of eye diseases that cause significant visual impairment and blindness, including neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), geographic atrophy (GA) and other retinal diseases. Genentech is also investigating platforms for sustained ocular drug delivery.
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
1Anti-VEGF/Anti-Angiopoietin-2 Bispecific Antibody RG7716 in Diabetic Macular Edema: Results from the Phase 2 BOULEVARD Clinical Trial. Presented by Dugel, P on 10th February during Session VII Diabetes, Retinal Degenerations, and Uveitis at the 2018 Angiogenesis, Exudation, and Degeneration meeting, Miami, Florida, USA.
2A Study of RO6867461 in Participants With Center-involving Diabetic Macular Edema (BOULEVARD). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02699450 . Accessed December 2017.
3Chakravarthy U BC, Brown D, Campochiaro P, et al. Phase 1 trial of anti–vascular endothelial growth factor/antiangiopoietin 2 bispecific antibody RG7716 for neovascular age-related macular degeneration. Ophthalmology Retina 2017.
4Rangasamy S, Srinivasan R, Maestas J, et al. A potential role for angiopoietin 2 in the regulation of the blood-retinal barrier in diabetic retinopathy. Invest Ophthalmol Vis Sci 2011;52(6):3784-3791.
5Bressler NM, Varma R, Doan Q, et al. Underuse of the Health Care System by Persons With Diabetes Mellitus and Diabetic Macular Edema in the United States. JAMA Ophthalmology. 2014 Feb;132(2):168-73.
6Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012;35(3):556-564.
7Bourne RR, Stevens GA, White RA, et al. Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health 2013;1(6):e339-349.
8Bhagat N, Grigorian RA, Tutela A, et al. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol. 2009;54(1):1-32.
9Barham R, El Rami H, Sun JK, Silva PS. Evidence-Based Treatment of Diabetic Macular Edema. Semin Ophthalmol 2017;32(1):56-66.
10Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology 2014;121(11):2247-2254.
11Granstrom T, Forsman H, Lindholm Olinder A, et al. Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting. Diabetes Res Clin Pract 2016;121:157-165.
12Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 Phase III randomized trials: RISE and RIDE. Ophthalmology 2012;119(4):789-801.
13Wecker T, Ehlken C, Buhler A, et al. Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD, DME, RVO and myopic CNV. Br J Ophthalmol 2017;101(3):353-359.
14Hariprasad SM, Mieler WF, Grassi M, et al. Vision-related quality of life in patients with diabetic macular oedema. Br J Ophthalmol 2008;92(1):89-92.